Wednesday, September 1, 2010

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.

A second human papillomavirus (HPV) recombi-nant vaccine has been approved by the FDA. GlaxoSmithKline's Cervarix.sup.™ contains antigens of oncogenic HPV types 16 and 18 and is produced with Baculovirus system in insect cells. It will be marketed to compete with Merck's quadrivalent Gardasil.sup.™ which is produced in yeast cells.

Indications

Cervarix is indicated for the prevention of cervical cancer, cervical intraepithelial neoplasia (CIN) grade 2 or worse, adenocarcinoma in situ (AIS), and cervical intraepithelial neoplasia (CIN) grade 1..sup.1 The vaccine is approved for use in females age 10-25 years.

Dosage

The recommended course is 3 doses given as an intramuscular injection at 0, 1, and 6 months. The vaccine is available as a single dose (0.5 mL) vial or pre-filled syringe.

Potential Advantages

Cervarix is formulated with an AS04 adjuvant system and appears to produce an enhanced immune response compared to the alum-based formulation (i.e., Gardasil)..sup.2 The ASO4 system is composed of a lipopolysaccharide from Salmonella typhimurium adsorbed on aluminum hydroxide in contrast to aluminum hydroxyphosphate sulfate. The vaccine also appears to provide better cross protection against HPV types 31, 33, and 45 than Gardasil..sup.3-5

Potential Disadvantages

Compared to Gardasil, Cervarix does not contain antigens for HPV-6 and HPV-11 and, therefore, does not protect against genital warts in females and males, or vulvar intraepithelial or vaginal intraepithelial neoplasia. Most common adverse events are pain, redness, and swelling at the injection site..sup.1

Comments

The efficacy of Cervarix is based on prevention of precancerous lesions (CIN2/3) or AIS associated with HPV-16 or HPV-18. In a study of 14,656 females (age 15-25 years) who were HPV-16 and HPV-18 DNA negative and seronegative at baseline and after the third dose, the vaccine was 92.9% effective (96.1% confidence interval [CI], 79.9-98.3) in preventing CIN2/3 or AIS compared to hepatitis A vaccine as the control..sup.1,3 The mean follow-up time was 39 months after the first dose. In a subset of patients who were negative for 14 oncogenic HPV types and received at least one dose of vaccine the efficacy was 98.4% (96.1% CI, 90.4-100). Cervarix was 52.8% effective in those with current infection or prior exposure to HPV-16 or HPV-18. It is not effective in patients who were positive for HPV-16 or HPV-18 at baseline. Cervarix provides > 75% cross protection against HPV-31 and HPV-45 and 45.7% against HPV-33, as defined by a 6-month persistent infection..sup.3,4 Gardasil provides 50% efficacy against persistent HPV-31 only and 40% for HPV-31/45..sup.4,5 Cervarix also produces higher antibody titer than Gardasil and higher cervicovaginal mucus-neutralizing antibody..sup.4

Clinical Implications

Cervarix is the second HPV vaccine approved for use in females and is estimated to protect against about 80% of cervical cancers. There are currently no published comparative trials. In placebo controlled studies, efficacies against HPV-16 and HPV-18 appear similar between vaccines..sup.1,5 Cervarix appears to be more immunogenic and provide better cross protection than Gardasil, but does not protect against genital warts. It is not known whether the ASO4 adjuvant system results in a longer duration of protection. The costs of the two vaccines are similar, $385 for 3 doses for Cervarix compared to $390 for Gardasil..sup.6